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Alan R Shalita

Publications and source records attributed to Alan R Shalita.

17 recordsLinked to original sources
PubMed2006

Neuropeptide (calcitonin gene-related peptide) induction of nitric oxide in human keratinocytes in vitro.

Nitric oxide (NO) is an important signaling molecule in both the central nervous system and the periphery, where it is involved in neurotransmission, vascular and bronchial tone, inflammation, and cutaneous immune function. More recently, NO has been implicated in intracellular signaling and may have a role in cellular differentiation, cytokine expression, and apoptosis. The experiments described herein examined the effect of calcitonin gene-related protein (CGRP), a cutaneous nerve neuropeptide, on NO production in human keratinocytes in vitro. CGRP stimulated two distinct increases in NO production: one within 30 minutes and a second at 24 hours. CGRP stimulated a modest increase in inducible nitric oxide synthase (iNOS) at 3-6 hours. Experimental evidence suggested that CGRP stimulated both constitutive NOS activity and generation of NO via nitrosothiol degradation within the first hour. Production of NO was paralleled by a decrease in nitrosothiol levels for 2 hour, suggesting that immediate NO release may originate from pre-existing stores. Nitrosothiols are ubiquitous molecules that comprise an important NO pool and have intracellular regulatory roles, particularly linked to oxidative stress. The present data indicate that, in addition to its known cAMP signaling pathway, CGRP may act to regulate keratinocyte biology through intracellular NO by modulation of S-nitrosothiol stores and stimulation of NOS activity.

Calcitonin Gene-Related Peptide↗
PubMed2006

Adapalene gel, 0.1%, as maintenance therapy for acne vulgaris: a randomized, controlled, investigator-blind follow-up of a recent combination study.

OBJECTIVE: To assess the maintenance effect of adapalene gel, 0.1%, relative to gel vehicle in subjects successfully treated in a previous 12-week study of adapalene-doxycycline, 100 mg, combination therapy. DESIGN: Multicenter, investigator-blind, randomized, controlled study. SETTING: Thirty-four US centers. SUBJECTS: A total of 253 subjects with severe acne vulgaris who showed at least moderate improvement from baseline (50% improvement from baseline) when treated with either adapalene plus doxycycline or doxycycline plus gel vehicle in a previous 12-week study. INTERVENTIONS: Subjects were randomized to receive adapalene gel, 0.1%, or gel vehicle once daily for 16 weeks. MAIN OUTCOME MEASURES: Efficacy and safety criteria included maintenance rate (subjects maintaining at least 50% improvement in lesion counts from previous therapy), lesion counts (total, inflammatory, and noninflammatory), global severity assessment, cutaneous tolerability, and adverse events. RESULTS: Adapalene maintenance therapy resulted in significantly larger maintenance rates (75% vs 54%; P<.001) and significantly lower lesion counts (total [P = .005], inflammatory [P = .01], and noninflammatory [P = .02]) compared with gel vehicle. Adapalene was safe and well tolerated in this study. Conclusion This study demonstrates a clinical benefit of continued treatment with adapalene gel, 0.1%, as a maintenance therapy for acne.

Acne Vulgaris↗
PubMed2006

Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, double-blind, randomized, parallel-group study.

OBJECTIVE: To evaluate the efficacy of 3 maintenance regimens (topical tazarotene, oral minocycline hydrochloride, or both) in sustaining improvement in acne. DESIGN: Multicenter, open-label treatment phase followed by double-blind, randomized, parallel-group maintenance phase. SETTING: Ambulatory patients in research or referral centers. PATIENTS: Volunteer sample of 189 patients with moderately severe to severe acne vulgaris (110 entered maintenance phase, 90 completed, and 2 discontinued because of adverse events). INTERVENTIONS: All patients were treated with 0.1% tazarotene gel (each evening) and a 100-mg capsule (twice daily) of minocycline hydrochloride for up to 12 weeks. Patients with 75% or greater global improvement at week 12 were randomly assigned to 12 weeks of maintenance therapy with tazarotene gel plus placebo capsules, vehicle gel plus minocycline capsules, or tazarotene gel plus minocycline capsules. MAIN OUTCOME MEASURES: Overall disease severity, global improvement, and lesion counts. RESULTS: All regimens were effective in sustaining improvements in acne. After 12 weeks of maintenance therapy, the mean reductions from baseline in noninflammatory and inflammatory lesion count, respectively, were 60% and 54% with tazarotene, 52% and 66% with minocycline, and 64% and 66% with tazarotene plus minocycline. At week 24, more than 80% of patients in each group had maintained a 50% or greater global improvement from baseline, and more than 50% had maintained a 75% or greater global improvement. CONCLUSIONS: A high percentage of patients with moderately severe to severe acne can maintain improvement in their condition with topical retinoid monotherapy. Maintenance with combination tazarotene and minocycline therapy showed a trend for greater efficacy but no statistical significance vs tazarotene alone. Topical retinoid monotherapy should be considered for maintenance to help minimize antibiotic exposure.

Acne Vulgaris↗
PubMed2006

Postinflammatory hyperpigmentation: evolving combination treatment strategies.

Postinflammatory hyperpigmentation (PIH) is a common acquired excess of pigment in the epidermal and/or dermal layers of the skin. Lesions persist for extended periods if untreated, thus therapy is warranted. Topical monotherapies include the standard bleaching agent hydroquinone (HQ) as well as retinoids. Recently, several fixed-dose combination products were introduced to the armamentarium: HQ 4%-retinol 0.15% in a microsponge formulation; HQ 4%-retinol 0.3%; mequinol 2%-tretinoin (RA) 0.01%; and fluocinolone acetonide (FA) 0.01%, HQ 4%, and RA 0.05%. Recent findings have suggested that mequinol 2%-RA 0.01% solution is a promising alternative for the treatment of PIH.

Adolescent↗
PubMed2004

Effects of tazarotene 0.1 % cream in the treatment of facial acne vulgaris: pooled results from two multicenter, double-blind, randomized, vehicle-controlled, parallel-group trials.

BACKGROUND: Topical retinoids are one of the most effective classes of topical drugs used to treat acne vulgaris. The effects of the gel formulation of the topical retinoid tazarotene have been widely reported, but few data on the cream formulation are available. OBJECTIVE: The primary aim of the 2 studies reported in this article was to determine the effects of tazarotene 0.1 % cream in patients with facial acne vulgaris. METHODS: Two randomized, double-blind, parallel-group studies were performed. The first was conducted at 14 investigational sites across the United States, and the second took place at 15 sites, with 5 of these providing blood samples for analysis of tazarotenic acid. In both studies, patients aged > or =12 years with facial acne vulgaris were randomized to receive tazarotene or vehicle cream QD for 12 weeks. Lesion counts (noninflammatory, inflammatory, and total) and overall clinical and global assessments were made at weeks 0 (baseline), 4, 8, and 12. Adverse events (AEs) were monitored throughout the study In one of the studies, therapeutic drug monitoring was performed at weeks 4 and 8 in members of the study population who gave consent for blood withdrawal. RESULTS: Eight hundred forty-seven patients were enrolled in the 2 studies (430 males, 417 females; mean age,19 years; age range, 11-52 years [1 patient was entered into the study at age 11 years, in violation of the protocol]). At 12 weeks, the median percentage changes from baseline in all 3 lesion counts were significantly lower with tazarotene than with vehicle (all, P < 0.001), as were the overall clinical and global responses (both, P < 0.001). Treatment-related AEs whose incidence was higher with tazarotene than with vehicle included desquamation, dry skin, erythema, a burning sensation on the skin, and skin irritation (all, P < 0.001) and pruritus (P < 0.01); most (83%-98%) were mild or moderate. Systemic exposure to tazarotenic acid was limited (mean, <0.1 ng/mL) and did not increase with time. CONCLUSIONS: In these 2 studies in adolescent and adult patients with facial acne vulgaris, tazarotene 0.1%cream QD for 12 weeks was effective and well tolerated. Systemic exposure to tazarotenic acid was limited.

Acne Vulgaris↗
PubMed2004

Benzoyl peroxide-based combination therapies for acne vulgaris: a comparative review.

Benzoyl peroxide, with its broad-spectrum antimicrobial activity, is among the most widely used topical agents in the treatment of inflammatory acne vulgaris. Benzoyl peroxide is marketed either alone or in combination with other topical antibiotics; namely, erythromycin and clindamycin. The combination products confer specific advantages over benzoyl peroxide alone, particularly in decreasing the in vivo follicular counts of Propionibacterium acnes, the anaerobic bacterium implicated in the pathogenesis of acne. In addition, the topical treatment of inflammatory acne has been complicated by the development of P acnes resistance to topical erythromycin and clindamycin. Combination products containing benzoyl peroxide and the topical antibiotics have been shown to both: (i) prevent the development of antibiotic resistance in acne patients; and (ii) confer significant clinical improvement to patients who have already developed antibiotic resistance.

Acne Vulgaris↗
PubMed2003

Lasers, light, and acne.

Acne vulgaris is a highly prevalent disease with significant potential for physical and emotional scarring. Acne lesions have long been noted to improve after exposure to sunlight. This improvement may be secondary to activation of endogenous porphyrins produced by Propionibacterium acnes. Recently, several investigators have presented studies in which light of particular wavelengths has been used to treat acne vulgaris. In this article, we review the results of these studies as we look to the future of light-based acne treatment.

Acne Vulgaris↗
PubMed2003

Current concepts in the treatment of acne: report from a clinical roundtable.

Acne vulgaris is the most common skin disorder in the United States, affecting approximately 17 million people. This figure includes 80% of all persons between the ages of 11 and 30 years, regardless of race, ethnicity, or gender (Kraning and Odland, 1979). Acne has a significant economic and social impact on doctor visits, medications, and absenteeism, as well as in the negative effect it can have on self-image and outlook, especially during the emotionally critical period of adolescence. Persons with acne may think of themselves as unworthy and socially unacceptable. Severe acne may lead to scarring and disfigurement, aggravating the already present psychosocial aspects of this condition. Because of the multifactorial nature of acne, current treatment options aim to modify one or more of its pathogenic factors. Clinical experience has shown that combination therapies, which affect multiple aspects of pathophysiology, are most likely to achieve this goal and help in its long-term management and resolution.

Acne Vulgaris↗
PubMed2003

Compared efficacy and safety of tretinoin 0.1% microsphere gel alone and in combination with benzoyl peroxide 6% cleanser for the treatment of acne vulgaris.

Our purpose was to evaluate the efficacy and safety of a combination of benzoyl peroxide 6% cleanser and tretinoin 0.1% microsphere gel versus monotherapy with tretinoin 0.1% microsphere gel. Eighty-seven healthy males and nonpregnant nonlactating females between the ages of 12 and 30 years with moderate inflammatory acne vulgaris were enrolled in this randomized controlled, investigator-blind, parallel group clinical trial. Subjects were evaluated over 12 weeks for a total of 4 visits. The investigators and subjects completed questionnaires about the test medications. Data from the 56 subjects completing the protocol were considered in the analyses of efficacy and tolerability. The reduction in inflammatory lesions from baseline was significant for both treatment groups at the end of the study. However, there was a significantly greater reduction in the group receiving the combination regimen. Both treatment groups had significant reductions from baseline in noninflammatory lesions at week 12, but no differences were observed between treatment groups. With the exception of skin tightness, which was significantly greater at week 12 in the subjects who received the monotherapy, there were no significant differences between the 2 treatment groups with respect to localized irritation. Adverse events were rare in all subjects. Not only did the combination regimen result in a greater reduction of inflammatory acne lesions than use of the monotherapy but also it did not result in an increase in local irritation.

Acne Vulgaris↗
PubMed2002

Acne vulgaris, I: pathogenesis and diagnosis.

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous units. It is a pleomorphic disorder with multifactorial pathogenesis. The many expressions of acne rarely present a diagnostic challenge, but correct classification of acne is crucial in choosing the appropriate therapies. Although previous research has provided a better understanding of the pathogenic factors, there is still a great deal to be learned.

Acne Vulgaris↗
PubMed2002

Acne vulgaris, II: treatment.

Treatment of acne vulgaris is based on a current understanding of the pathogenic factors. Effective management can be achieved for each individual patient using a variety of the powerful weapons in our therapeutic arsenal.

Acne Vulgaris↗
PubMed2002

Acne 2002.

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Acne Vulgaris↗
PubMedDate not supplied

Acne: clinical presentations.

Acne vulgaris, the most common disease of the skin, can be manifested in a wide variety of clinical presentations. As a result of this clinical variation, there are almost as many classifications of acne as there are clinicians with particular interest in the disease. Thus acne has been classified as types I-IV, inflammatory versus noninflammatory, comedonal, comedopapular, papular, papulopustular, pustular, and "cystic" or nodular (even nodular-cystic). For those who are enamored of classification, there are subdivisions of the various categories, including "sandpaper comedones" and microcysts. There is even disagreement as to what constitutes a papule versus a nodule. The classic textbook definition of a nodule refers to lesions 1 cm or larger, but the early investigators of oral isotretinoin defined nodules as 4 mm or larger, and this definition has creeped into many texts, recently clarified by Bologna.(1)

Acne Vulgaris↗
PubMedDate not supplied

Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study.

BACKGROUND: Combination therapy with a topical retinoid and an antibiotic is recognized as a rational and effective approach for the treatment of acne vulgaris. Adapalene, a naphthoic acid derivative with anti-inflammatory and receptor-selective retinoid properties, is safe and well tolerated. While the combination of adapalene with oral or topical antibiotics has been shown to deliver a superior and faster response than an antibiotic alone, the clinical benefits of a combination of adapalene and doxycycline, the most frequently prescribed oral antibiotic for acne in the United States, have yet to be evaluated. OBJECTIVE AND METHODS: In a 12-week study, the efficacy and safety of the combination of adapalene gel 0.1% with doxycycline was compared with doxycycline alone for the treatment of severe acne. Subjects were randomized to receive doxycycline once daily in the morning and either adapalene or vehicle once daily in the evening. RESULTS: At Week 12, the combination adapalene-doxycycline was significantly superior to doxycycline alone for change from baseline in total (p<0.001), inflammatory (p=0.02), and noninflammatory (p<0.001) lesions. Significant differences in total lesions were observed as early as Week 4 (p=0.04). Both treatments were well tolerated, and no serious adverse events were reported. CONCLUSIONS: The study demonstrates that the combination of adapalene and an oral antibiotic provides a superior and faster benefit than antibiotic therapy alone and should be considered at the initiation of treatment.

Acne Vulgaris↗
PubMedDate not supplied

The safety and efficacy of clindamycin phosphate foam 1% versus clindamycin phosphate topical gel 1% for the treatment of acne vulgaris.

Clindamycin phosphate is the most widely used topical antibacterial agent for acne treatment. Treatment of patients with mild to moderate acne vulgaris with a new foam formulation (clindamycin foam, CF) for 12 weeks was at least as effective as clindamycin gel (CG) based on the Investigator's Static Global Assessment (ISGA) score. CF was superior to CG based on the reduction from baseline in total (P = .0014), inflammatory (P = .0478), and noninflammatory (P = .0037) acne lesion counts. Additionally, CF achieved efficacy that was superior to that of vehicle foam based on ISGA score (P = .0025) and all 3 lesion counts (all P < .05). Adverse experiences in the active treatment groups were mild or moderate and transient in nature. Thus the foam formulation of clindamycin is a safe and effective acne treatment; the unique foam delivery vehicle may offer cosmetic benefits to the patient and thus increase compliance.

Acne Vulgaris↗
PubMedDate not supplied

Anti-inflammatory properties of narrow-band blue light.

BACKGROUND: Narrow-band blue light (420 nm) has demonstrated safety and efficacy in the treatment of acne vulgaris. It works by exhibiting a phototoxic effect on the heme metabolism of Propionibacterium acnes. Previous studies using blue light showed more improvement in inflammatory lesions than in comedones, as well as some improvement on the untreated side. Cytokines have demonstrated a critical role in the development of inflammation. The expression of pro-inflammatory cytokines such as IL-1alpha have been shown to result in the expression of vascular and dermal adhesion molecules, the chemoattraction of inflammatory cells, and the stimulation of other inflammatory mediators. In addition, UVB radiation serves as a potent modulator of cell-mediated immune responses. PURPOSE: This study investigated the effect of narrow-band blue light on the inflammatory process in the presence and absence of cytokines and UVB using IL-1alpha and ICAM-1 as markers for inflammation. METHODS: Two immortalized keratinocyte cell lines were compared: HaCaT, produced by spontaneous immortalization of a genetically altered cell line, and hTERT, obtained by stable transfection of primary cell culture with human telomerase reverse transcriptase. Cells were treated with INF-y and TNF-alpha and exposed to UVB (312 nm at 50 mJ/cm2) and/or blue light (420 nm at 54 mJ/cm2 and 134 mJ/cm2). The expression of IL-1alpha and ICAM-1 was measured by quantitative ELISA. RESULTS: The results showed that blue light and low-dose UVB treatment of HaCaT and hTERT cells resulted in inhibition of cytokine-induced production of IL-1alpha. The level of IL-1alpha decreased by 82% in HaCaT and by 75% in hTERT cells when exposed to blue light. It decreased by 95% in HaCaT and by 91% in hTERT cells when blue light was used in combination with UVB. ICAM-1 expression was similarly reduced in HaCaT, but not in hTERT cells. CONCLUSIONS: This study showed that narrow-band blue light has anti-inflammatory effects on keratinocytes by decreasing the cytokine-induced production of IL-1alpha and ICAM-1. In addition, blue light demonstrated synergistic effects with low-dose UVB light. These results expand the properties of narrow-band blue light in modulating the inflammatory process and will facilitate testing of its phototherapeutic applications in different inflammatory skin conditions.

Acne Vulgaris↗